Adjuvant and neoadjuvant chemotherapy is increasingly being used in the treatment of breast cancer patients. However, drug resistance plays an important role in chemotherapy failure in this cancer. The aim of this study was to determine the correlation between technetium-99m sestamibi (Tc-99m MIBI) breast imaging results and expression of the drug resistance proteins (p-glycoprotein (Pgp), Ki-67 and mutant p53) in human breast cancer tissues. Twenty-four breast cancer patients underwent Tc-99m MIBI breast imaging before surgery or biopsy. Protein expression was investigated by immunohistochemical studies on multiple nonconsecutive sections of surgery or biopsy samples. Tumor to background (T/B) ratios calculated by Tc-99m MIBI breast imaging were correlated with protein expression determined by immunohistochemical studies. The T/B ratios were significantly lower in 8 patients with positive Pgp expression (Group 1) when compared with 16 patients with negative Pgp expression (Group 2) (1.40 +/- 0.11 and 2.76 +/- 0.60, p < 0.05). However, the differences of T/B ratios between the patients with positive and negative Ki-67 mutant p53 expression were not significant. Our data confirmed that Tc-99m MIBI breast imaging is useful for determination of the presence of Pgp expression in breast cancer patients. No significant relationship between Tc-99m MIBI breast imaging results and Ki67/mutant p53 was found.